The identification of therapeutic or prophylactic compounds that may be useful for treating or preventing ocular diseases and disorders while exhibiting low toxicity and/or side effects is a focal point of drug discovery and development. Evaluation of the potential impact of drug candidates on human and animal health is a major component of the risk/benefit assessment. A number of cell-based in vitro efficacy and toxicity screens have been developed; these screens, however, do not permit evaluation of the therapeutic and toxic effects of a compound in vivo on an intact animal. Notably, cell-based assays are designed at the molecular and cellular levels. As a result, determining the impact of a compound of interest on higher levels of cellular organization, such as on an intact eye, or during eye (ocular) development, requires whole animal testing. In addition, current screens do not permit the assessment of compound effects on other potential target cells, tissues and organs of an animal together with those effects on the eye, simultaneously or over time. Thus, there is a need for cost-effective, comprehensive methods for screening compounds for in vivo ocular activity.
Zebrafish are used as a small animal model in which to screen compounds for biological activity such as, for example, angiogenesis activity, cell death activity, and/or toxic activity. (See, e.g., U.S. Pat. Nos. 6,299,858 and 6,656,449, the disclosures of which are incorporated herein in their entirety for all purposes.) Compared with conventional animal models, zebrafish provide several advantages, including, for example, short assay times, easy animal maintenance, need for smaller quantities of compounds, single dosing of compounds, ease of administration of compounds, quantitative assays, ease of obtaining a statistically significant number of animals per test, and suitability for large-scale screening of compounds (See, e.g., Norrby, J. Cell. Mol Med. 10:588-612, 2006; U.S. Pat. Nos. 6,299,858 and 6,656,449). The present invention relates to the use of zebrafish and other teleosts to screen agents for ocular activity, as well as for cell death and/or toxic activity in target tissues and/or organs from a whole, live animal in vivo.